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Functional interaction between PARP‐1 and PARP‐2 in chromosome stability and embryonic development in mouse
Author(s) -
Ménissier de Murcia Josiane,
Ricoul Michelle,
Tartier Laurence,
Niedergang Claude,
Huber Aline,
Dantzer Françoise,
Schreiber Valérie,
Amé JeanChristophe,
Dierich Andrée,
LeMeur Marianne,
Sabatier Laure,
Chambon Pierre,
de Murcia Gilbert
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg206
Subject(s) - biology , embryonic stem cell , poly adp ribose polymerase , genetics , microbiology and biotechnology , dna , polymerase , gene
The DNA damage‐dependent poly(ADP‐ribose) polymerases, PARP‐1 and PARP‐2, homo‐ and heterodimerize and are both involved in the base excision repair (BER) pathway. Here, we report that mice carrying a targeted disruption of the PARP‐2 gene are sensitive to ionizing radiation. Following alkylating agent treatment, parp‐2 −/− ‐derived mouse embryonic fibroblasts exhibit increased post‐replicative genomic instability, G 2 /M accumulation and chromosome mis‐segregation accompanying kinetochore defects. Moreover, parp‐1 −/− parp‐2 −/− double mutant mice are not viable and die at the onset of gastrulation, demonstrating that the expression of both PARP‐1 and PARP‐2 and/or DNA‐dependent poly(ADP‐ribosyl) ation is essential during early embryogenesis. Interestingly, specific female embryonic lethality is observed in parp‐1 +/− parp‐2 −/− mutants at E9.5. Meta phase analyses of E8.5 embryonic fibroblasts highlight a specific instability of the X chromosome in those females, but not in males. Together, these results support the notion that PARP‐1 and PARP‐2 possess both overlapping and non‐redundant functions in the maintenance of genomic stability.